PXD055878

PXD055878 is an original dataset announced via ProteomeXchange.

Title	The SIRT1 activating compound SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery
Description	Duchenne muscular dystrophy (DMD) is a rare and devastating genetic disorder, whose management is still a major challenge, despite progress in genetic and pharmacological disease-modifying treatments have been made. Mitochondrial dysfunctions contribute to DMD, however, there are no effective mitochondrial therapies for DMD. SIRT1 is a NAD+-dependent class III histone deacetylase that controls several key processes and whose impairment is involved in determining mitochondrial dysfunction in DMD. In addition to well-known resveratrol, other potent selective activators of SIRT1 exist, with better pharmacokinetics properties. Among these, SRT2104 is the most promising and advanced in clinical studies. Here we unveil the beneficial effects of SRT2104 in flies, mice, and patient-derived myoblasts as different models of DMD, demonstrating an anti-inflammatory, anti-fibrotic, and pro-regenerative action of the drug. We also elucidate, by molecular dynamics simulations, that a conformational selection mechanism is responsible for the activation of SIRT1. Further, the impact of SRT2104 in reshaping muscle proteome and acetylome profiles has been investigated, highlighting the drug as an attractive exercise mimetic for the treatment of DMD. Overall, our data suggest SRT2104 as a possible therapeutic candidate to successfully counteract the progression of the dystrophic phenotype in DMD.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_02:54:26.082.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD055878
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Erica Gianazza
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-16 01:18:21	ID requested
⏵ 1	2025-05-07 02:54:26	announced

10.1038/s41419-025-07595-z;

Giovarelli M, Zecchini S, Casati SR, Lociuro L, Gjana O, Mollica L, Pisanu E, Mbissam HD, Cappellari O, De Santis C, Arcari A, Bigot A, Clerici G, Catalani E, Del Quondam S, Andolfo A, Braccia C, Cattaneo MG, Banfi C, Brunetti D, Mocciaro E, De Luca A, Clementi E, Cervia D, Perrotta C, De Palma C, The SIRT1 activator SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery. Cell Death Dis, 16(1):259(2025) [pubmed]

10.6019/PXD055878;

submitter keyword: metabolism,muscular dystrophy, SIRT1, mitochondria

Clara De Palma
contact affiliation	Dept of Medical Biotechnology and Translational Medicine,University of Milan, Milan
contact email	clara.depalma@unimi.it
lab head
Erica Gianazza
contact affiliation	Centro Cardiologico Monzino
contact email	erica.gianazza@cardiologicomonzino.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055878
     1. Label: PRIDE project
     2. Name: The SIRT1 activating compound SRT2104 exerts exercise mimetic effects and promotes Duchenne muscular dystrophy recovery